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  • Open Access

Clonality of HTLV-1 differs between infected CD8+ T cells and infected CD4+ T cells in vivo

  • 1,
  • 2 and
  • 1
Retrovirology201411 (Suppl 1) :P137

https://doi.org/10.1186/1742-4690-11-S1-P137

  • Published:

Keywords

  • Integration Site
  • Proviral Load
  • Minor Population
  • Median Proportion
  • Proviral Integration

HTLV-1 selectively infects CD4+ T cells in vivo, with a minor population carried in CD8+ T cells. We previously established a method for the analysis of the clonality (clone frequency distribution) of infected cells by mapping and quantifying HTLV-1 proviral integration sites using high-throughput sequencing (Gillet et al, Blood, 2011; Cook et al, Blood, 2012; Melamed et al, PLoS Pathogens, 2013). To test the hypothesis that the clonality of HTLV-1 differs between infected CD8+ T cells and infected CD4+ T cells in natural infection, we magnetically sorted CD4+ and CD8+ T cells from PBMCs of 12 HTLV-1-infected individuals: 6 patients with HAM/TSP and 6 asymptomatic HTLV-1 carriers. We then used our high-throughput sequencing technique to quantify HTLV-1 clonality in each cell population. The median proviral load in CD4+ T cells and CD8+ T cells was 12.3 copies (range 6.0-30.2) and 2.0 (1.1-6.2) copies per 100 cells, respectively. The median proportion of the load carried by the infected CD8+ cells was 5.0% (2.3%-35.3%). Proviral load in CD8+ cells and in CD4+ cells significantly correlated with proviral load in total PBMC (p<10^-6 and p<10^-3, respectively). The clone frequency distribution was significantly more oligoclonal in CD8+ cells than in CD4+ cells: infected CD8+ clones were significantly over-represented among the most abundant clones in the blood. We conclude that HTLV-1-infected CD8+ T cells have a clonal distribution distinct from infected CD4+ cells. These results show that infected CD8+ T cells contribute disproportionately to the high PVL seen in HTLV-1 infection in vivo.

Authors’ Affiliations

(1)
Section of Immunology, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, UK
(2)
Section of Infectious Diseases, Imperial College London, Wright-Fleming Institute, Norfolk Place, London, UK

Copyright

© Melamed et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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